ACR24 RA Panel Key Discussions on Rheumatoid Arthritis Save
Panelists: Dr. Jonathan Kay, Dr. Jiha Lee, Dr. Eric Dein and Dr. Jeffrey Sparks
Transcription
Hello, I'm Jonathan Kay from UMass Chan Medical School in Worcester, Massachusetts. Welcome to the ACR Convergence twenty twenty four Rheumatoid Arthritis Panel, during which we'll review for you highlights about rheumatoid arthritis from ACR Convergence twenty twenty four, which just concluded in Washington, D. C. I'm joined here by three esteemed colleagues, and I'll ask you to introduce yourselves. Eric?
Yes. Hi, I'm Eric Dyne. I'm from Atlantic Health in Summit, New Jersey.
Jeeha?
Hi, my name is Jeeha Lee. I'm a rheumatologist from University of Michigan.
And finally, Jeff.
Hey, everyone. My name is Jeff Sparks. I'm a rheumatologist at Brigham Women's Hospital and Harvard Medical School in Boston, Massachusetts.
Excellent. So for the first round, each of us is going to pick our favorite abstract. So Eric, what piqued your interest?
So I'm going to talk about abstract seventeen forty five. I think there I don't know if there's oral surveillance fatigue after talking about it endlessly at our prior conferences, but I thought there was one post hoc analysis looking back at it that I thought was useful and changes the way I think about that data a little bit. And so, this was looking at, of course, who have been following know that the oral surveillance was looking at tofacitinib versus adalimumab. And of course, that main takeaway is that there was the higher cancer and MACE event in those at risk patients on tofacitinib compared to TNF inhibitor like adalimumab. That, of course, has had a lot of conversation, the black box warning, and a lot of conversation who is appropriate for tofacitinib and how do we interpret that slightly higher increased risk.
One thing that I thought was interesting was when they specifically looked at the statins usage of patients on it. This is a study that was enriching for patients at the highest risks that were they were looking for outcomes, and yet under a quarter of them were on a baseline statin. Of patients in the study who had known ASCVD, so should be on a statin, Only fifty three percent were on it, so about half of them were on it. Only about fourteen percent of people were on the high intensity ideal statin. So it was certainly not optimized in these patients in a clinical trial.
And I thought what was interesting, the main kind of takeaway of it, is that when you look at the patients who were on a statin in the tofacitinib group compared to the people on the statin in adalimumab, so ideally the people who are getting the ideal management, there wasn't a difference in MACE events. What does this mean? Think kind of the first takeaway is we need to be doing more to make sure that we're doing that baseline therapy. Of course, when we go into these post hoc analyses, you're cutting and dicing the numbers in all sorts of different ways and you could find all sorts of noise in the numbers. So, I want to take this as absolute faith, but it is reassuring to say that if we're managing the comorbidities and we're doing all the preventative things, maybe that might mitigate it.
And when we're thinking about weighing the risks and benefits in a patient who we think may be on a JAK inhibitor or appropriate for a JAK inhibitor but has some risk factors, would, as I'm weighing that, I would say, let's at least make sure that we're doing that right therapy. So, I think that's an interesting way to look at that study and those risks.
So that's an interesting study. It reflects that rheumatologists are not necessarily doing a great job of putting our patients on statins, But rheumatologists are quite busy. And in the twenty minutes that you have with a patient with rheumatoid arthritis who's on methotrexate and probably another disease modifying antirheumatic drug, you know, do you have time to talk about the statins and talk about everything else? We should. But I think we're all in the dark about that.
And Eric, it looks like you're in the dark, too. But as you come into the light, rheumatologists should come into the light and think more about prescribing statins for patients with rheumatoid arthritis at increased risk for cardiovascular disease, at least those taking a JAK inhibitor. Jeff, what are your Well,
first off, I chatted with John about this and he promised me it would be the last oral surveillance post hoc analysis. I'm gonna hopefully hold him to that, but I doubt that, but probably be a lot more. I have to say, it's pretty shocking that patients enrolled into a clinical trial for cardiovascular disease, the outcome that so few people were on statins that should have been. And we all know it's even worse in clinical care. And these are complex patients.
They're falling through the cracks. They get fragmented care. So obviously a huge opportunity to get patients to get treated appropriately. And I think as Eric hit the nail on the head, I think you feel a lot more reassured to start a JAK inhibitor in someone that's on a statin. So I think this is a really high impact abstract.
Absolutely, geeha.
No, I agree with that. And I think one of the themes I saw throughout ACR was more and more emphasis about treating the whole patient, really taking into the fact all their multimorbidity. That's one of the things that Doctor. McGinnis talked about even starting at the review course, because there's data to show with each multimorbidity effectiveness, the DMARs go down and also our patients become more difficult to treat with more, not only just the disease activity related burden, but also the uncontrolled symptoms like fatigue and pain. So I think overall I hear and resonate with you that it's sometimes perhaps out of the scope rheumatology, given the time limited barriers we have, but this is all the more reason why generating this data is important, but then to be able to have something embedded in our electronic health record system that makes it easier to identify these patients, but actually really design care models that allow for a comprehensive care model.
And oral surveillance enrolled older patients. So these are patients who not only have rheumatoid arthritis, but having been around for at least fifty years and having at least one cardiovascular risk factor, this is a patient population that we should pay specific attention to. So especially in the older patient, although I regard 50 as being rather young, but it's all relative. But that's a population in which we should do a better job of reducing cardiovascular risk. While we're on the topic of cardiovascular risk, I might as well take a shot at my abstract.
I'm going to pick abstract number 2,673, which was presented at the oral rheumatoid arthritis treatment session, the last session of the meeting on Tuesday morning between 11AM and 12:30PM. John Giles and I co chaired that session. And this was an abstract from British Columbia. It was an abstract that looked at changes in mortality risk after stopping glucocorticoids. In British Columbia, there's a single payer and a large population based cohort of patients with rheumatoid arthritis.
They took this population based incident rheumatoid arthritis cohort of patients who met the definition of having rheumatoid arthritis using nineteen eighty seven ACR criteria between 01/01/1996 and December 3133. So in 2010, the ACR ULAAR criteria came out, but this used the older ACR criteria. And they used billing data that followed these patients until the December 2018. And they looked at oral glucocorticoid exposure, yes or no. And they looked at deaths with cardiovascular disease or infections as the primary cause, identifying those from death certificates.
And they looked at the risk of death associated with cumulative duration of glucocorticoid use and time since glucocorticoid cessation. And what was most impressive, the key finding was that the mortality due to cardiovascular disease or due to infections never returned to normal for individuals who had been taking glucocorticoids for longer than two years in terms of cardiovascular death or for longer than three years in terms of infections. So, if you'd use glucocorticoids for six, twelve, or twenty four months for cardiovascular deaths, your risk returned to the level of those who've never been exposed to glucocorticoids at two point five years for those who'd been treated with glucocorticoids for six months, three point five years for those who'd been treated for one year, and at five point five years for those who had been treated for two years with glucocorticoids. But the most impressive finding was that if you'd been on glucocorticoids for longer than two years and certainly longer than three years, the increased mortality risk from cardiovascular disease and infection persisted. So glucocorticoids are not trivial in the least.
The infection related mortality increased by seven point five percent for every year of glucocorticoid use and decreased by one point three percent for every year after stopping glucocorticoids. That from infections increased by six point eight percent for every year of glucocorticoid use and decreased by four point nine percent for every year after stopping glucocorticoids. So patients who are treated for just a brief six month period, which is not uncommon to control disease activity in someone starting disease modifying antraumatic drug, those patients have significantly increased cardiovascular death and also death due to infections. So we have to be very mindful of the potential risks that we're imparting by prescribing glucocorticoids. And we have to be as prompt as possible in discontinuing these medications.
This was a concurrent session, but this abstract certainly has the impact that it should have been a plenary.
I agree. I think there was actually a scientific session about envisioning a steroid free remission and the topic wasn't just about RA, but there was discussion around vasculitis as well as lupus. So this shift in terms of recognizing that steroids, that it's not just the duration, but that even at very low doses, and also like this study pointed out that there are long lasting negative effects is becoming recognized. Michele Petrie in the lupus literature said for every one milligram, there's a three percent increased risk of organ damage. And like one milligram, that's pretty trivial.
And one of the things I took away from this study and that session discussion is that continuation is an action that if we don't pay attention to the medication they're beyond, and then we might be missing opportunity whereby escalating therapy, they would have better chances of tapering off of steroids. Beth Wallace studies this area, and she's shown time and again that tapering is really challenging, not just because of adrenal sufficiency related reasons, but they also develop steroid withdrawal symptoms that are quite different from disease activity. So there's a lot of challenges. We don't know how yet to get there. So I think what's important is for us to recognize that we need to reduce the pipeline so that less people end up on these low dose steroids.
So that means earlier on, we need to really make sure that we assess the burden and treat patients according to the newer regimens that are available. Because I think, Jeff, you did this study to show that there were actually very habitual. No matter how many new DMARs are introduced into the market, HUMIRA has the largest share and there's a delay of any new DMARs and then the numbers really don't blip. That was really fascinating for me.
I'm glad you used the term habituals because I was going to say that corticosteroids are addictive. They are. And I have a patient who called me yesterday. I started him on methotrexate. He was new onset rheumatoid arthritis.
I started him on methotrexate about four or five months ago. Initially treated him with methotrexate escalated quickly to twenty five milligrams a week, put him on a TNF inhibitor. After three months on alimab, his disease remained active. So I switched him I put him in the RA proper study. So the study randomized him to a non TNF biologic rather than a JAK inhibitor.
But I put him on abatacept. And he's only been on abatacept for about a month, but he called up saying that his hands were miserable. He's a tailor, and he has to work with his hands, and he's been unable to work for the week. So I put him on steroids. But he's been on a number of steroid tapers because he can't function and can't work without that.
But the impact that the steroids that I'm prescribing in the best interest of the patient are also not in his best interest in terms of increasing his risk of cardiovascular and death from infection cardiovascular death and death from infection. So I certainly want him to live and I want him to be comfortable. But it's we're really navigating a narrow channel between Scylla and Charybdis as did Adesha's in Odyssey.
I love it. Wow.
Anyhow, Jeff, you've got an abstract there.
Well, was just going to chime in that, you know, I think this has been the theme over the last five, ten years. You know, it reminds me of the Ralph Nader book, Unsafe at Any Speed. And we'd love to hate steroids, but it seems like we haven't put a dent in it. And part of this is going back to the guideline debate, ACR, I was on that guideline and we, I think bravely said that the default should not be to use glucocorticoids and many other guidelines say you should use it. And I think everyone knows that there's long term toxicity, but I think you can't be a long term user unless you start.
So short term glucocorticoid use as a gateway drug, if you will. So anyway, I think this is the eternal debate in rheumatology about love and hate relationship with steroids.
Well, we're giving the initial dose of crack cocaine. You put the patient on
I'm not prescribing that. Just
No, not literally, but we're the dealer. We're giving them a taste of what it's like.
We should give them less refills, perhaps.
Yeah. I think Johnstone Cold Steroids are a necessary evil in rheumatology.
Yeah, Doctor. Petrie always says that the P is for poison, for prednisone.
They seem impervious to all this bad press. I don't know if there's any other analogy going on.
Well, and I don't give refills on methotrexate prescriptions. I'll give a ninety one day prescription that'll last just thirteen weeks. But we ought to think very carefully as you suggested that we not give refills on prednisone and that we reassess each time that we're refilling a corticosteroid prescription.
And patients will stockpile is the other kind of big takeaway from that scientific session is when you start prednisone, have to have an end date, you have to have a plan. They talk about withdrawing or tapering quickly, withdrawing the last doses more slowly so that you're dealing with those withdrawal effects. But really having a plan, knowing how much they have, how much they're taking so that they don't have these emergency supplies so that they're self medicating.
Yeah. And I think that's important, like you said, making sure to have an awareness and document, because actually now documenting a taper plan is a CMS quality measure. So there's a system level recognition of this issue, and there's gonna be, I think, more scrutiny and efforts to be able to address this, not just for rheumatology, but across the board.
So the patient who asks to have a Medrol dose pack in reserve, just in case they have a flare, we should probably think very carefully before writing that prescription.
Yep.
So Jeff, you've got another abstract there.
All
right. Well, I couldn't resist an RAILD abstract. I'm sorry. But I am gonna talk about abstract number seventeen thirteen. I think this was the most important abstract for RA at the meeting.
This was about treatment of RA ILD with biologic and targeted synthetic DMARDs. So this is VA data led by the Nebraska group with Bryant England, and, you know, they're doing great work. And they looked at their VA database. As we all know, it's more men, it's more smokers. So maybe not generalizable, but it's really enriched for RAILD.
So it's a great data set for that. So they previously validated methods to find RAILD, and in this analysis, they looked at new users of biologic and targeted synthetic DMARDs who had RAILD and did target trial emulation. For those that don't know, this is kind of the cutting edge epidemiologic technique to try to really use observational data to do as best as you can to do kind of a head to head comparison, kind of a dream RCT, if you will. So in this study, they looked at all the different mechanisms of action, compared it to rituximab. As a side note, the 2023 ACR chest guidelines, recommended rituximab as first line treatment for RA ILD, and none of these other medications were recommended as first line treatment, so we really need some data here.
And really, the the bottom line is is that there were no statistical, associations with the outcomes, which were very important outcomes of respiratory hospitalization or overall mortality. So that's comparing abatacept to rituximab, comparing, IL-six receptor inhibitors to rituximab, and comparing abatacept, TNF inhibitors, as well as JAK inhibitors. So no difference whatsoever across all of those categories. And certainly it could be underpowered. It could be a hard outcome to hit.
It could be that all the drugs we're using actually work to prevent these bad outcomes. It could be that none of them work. And certainly it could be related to confounding where maybe even though these patients have RALD, there's certainly a spectrum of severity. Maybe some people are more active in the joints and they're choosing one of the meds for that. Maybe the rituximab's treating the really, really bad RA ILD.
But I think it's really the most comprehensive analysis that's been done looking at DMARDs and RA ILD treatment. And as an aside, our group recently reviewed all of the trial data that informed the, ACR chest guidelines. And even though RA is our most common disease, this is one of the most serious manifestations. There's actually only ever been three trials that have enrolled any RALD patients into a prospective trial. So, to me, it's just, you know, huge, huge, opportunity and gap in literature because we're certainly confronted with these patients and certainly our group and others are moving towards trial, and this will be a great sort of lead into that.
Excellent. So it doesn't really matter what you choose as long as you're treating the disease.
You know, I think the optimist view is that, and I have to say the pulmonologists say this as well, you know, they have RA that's driving the lung disease. If you treat the RA successfully, that's also going to treat the lungs. I think that's the optimistic view. I think the pessimistic view is that none of them work. And again, I think another certainly possible outcome is that perhaps it's a confounding issue where the really bad patients got rituximab and maybe it helped those patients and then the very mild patients got the alternative drugs and it didn't really, there wasn't much to be needed as far as to be helped.
So, yeah, like I said, I think it's a really nice framework that leads to kinda more definitive trials, and we really need it, honestly. We have a few antifibrotics, but, you know, this is not an uncommon, thing to be confronted with in care. And it's just really frustrating, as you know, to see these patients, you know, progress into worse and, you know, we're not sure how our drugs are helping or hurting in the end.
Well, to get back to anecdotal medicine, I have a patient with rheumatoid arthritis. I've followed him probably about twenty years and he was doing fine on methotrexate and on, I think, etanercept. And all of a sudden he had some shortness of breath and went to the local hospital, was found to have ILD. And now he's in hospice care.
Yeah. It's really humbling when you see this. Yeah, it's really, really tough.
And I treat rheumatoid arthritis disease activity aggressively, so his RH disease activity was well controlled. Yeah. I could have done more for him.
Yeah, certainly it's more complicated than just, you know, treating to target, getting them into remission from a joint standpoint. We certainly see many patients that continue to have lung disease.
Are there any of the biologic DMARDs that might have a little bit worse safety profile in terms of lung disease?
Well, you know, TNF inhibitors have probably a reputation for not being good for the lungs and probably not helping. And actually the same group last year did a very similar abstract that was presented at the plenary looking at TNF inhibitors versus alternative biologics, and they also did not find any difference in outcomes. And, again, I think it is reassuring when you have to reach for it to have some data saying that this isn't gonna, you know, really blossom their ILD and worsen things. But, you know, during the day, we really wanna know what's gonna treat it and what's the best option.
Well, we look forward to the excellent work that's coming out of your group and look to you and your colleagues for leadership. So Jihai, your last abstract in the first round before the lightning round. So what happens in your interest?
Yeah. So Justice Jack is partial to ILD. I am partial to aging related issues in rheumatology. So I'm going to discuss abstract number 2,224, which looks at the age of onset of RA and radiographic changes. This study used data out of, Brigham, but interesting, the first author is, from Japan, which I think is meaningful because Japan has one of the oldest aging populations, so they actually have a lot of data about this.
So this study focused on an entity known as late onset RA, which means a person is diagnosed with RA typically over the age of 65. And they had a longitudinal cohort, called BRAS, the Brigham Women's Hospital Rheumatoid Arthritis Sequential Study, which is a single center, large RA registry, which means you have disease activity measures demographics. This is valuable because older adults are usually excluded from clinical trials, so to be able to have a data set where you can directly compare older adults to younger provides value because otherwise you're limited to using claims or administrative data to study older adults in that regard. And so what they were specifically interested in was are there differences in terms of incident radiographic changes? And the reason is because this entity of late onset started actually appearing in the literature Okay, Google.
Okay,
Google, turn on lights.
1950s to the 1960s. But we really don't recognize this in clinical practice. But then last year, our European colleagues published paper looking at incidents of rheumatic diseases across the board. They had more than two million patients, registered, and it showed that the peak incidence of RA has somewhat shifted, and we're seeing people diagnosed actually into their 70s and 80s. So there's a growing group of older adults newly being diagnosed with RA, and we know they have very different clinical presentations.
They tend to have more acute onset, systemic presentations, large joint involvement, CR negativity. And we talked earlier about, multimorbidity and it's pulling the challenge for us as rheumatologists because we're having to introduce high risk medication to an older adult who already has existing multimorbidities. So I think this population in particular poses interesting challenges. And what they found is they had patients diagnosed based on their age of already diagnosis, split them up as young if they were diagnosed on 44 years of age or younger, middle if they were 45 to 65, and anybody diagnosed after the age of 66 was considered late onset. And in that group for that late onset, the average age was around 72.
And what's interesting is that when you become late onset, the sex disparity that we typically see in the younger population kind of diminishes. So about fifty percent were female in that late onset group compared to like eighty to ninety percent in the younger two age groups as well. And as I mentioned before, they tend to be more seronegative if they have late onset RA. This group did have higher disease activity measures on diagnosis, but at the same time they were less likely to receive DMARS, especially biologics or targeted synthetics. So only about ten percent of the late onset RA were on biologics, whereas the younger groups, about twenty to twenty five percent were on it.
And conversely, that also meant that the late onset group were more on steroids, about fifty percent were on steroids as opposed to only about a third, in the younger age groups. In terms of that outcome that they were interested in terms of erosions, when they did, odds ratio calculations and multivariable analysis compared to the young onset, the late onset were eight times more likely to have erosive changes near and at the time of diagnosis. And this actually persisted even when they adjusted for treatment. So when you were without any treatment, the odds went down a little bit to six, but if you didn't, it went up to 10. So there's still quite of a disparity in terms of disease severity in terms of presentation based on disease activity, but unknowingly they also are going to be more likely to approve erosion and damage.
So I think that it's important to recognize that this entity exists in terms of late onset RA, that they can have very different presentation. Not included in this paper, but reported in others, is that there's a lot of overlap with PMR, about a third have that phenotype, and another third will actually have OA type phenotype. So that can lead to delays in diagnoses. But I think that awareness is going to allow us to say, okay, this is also another population where we need to check some of our biases because there was a study where, the rheumatologist said erosions are, they consider erosion to be as important as age in terms of determining treatment decisions. But if you see the older number age, they're four times likely to initiate any kind of DMARC.
So I think we need to start recognizing how we perceive age, that it's not just a number, but to ensure that we actually introduce treatments in this population and start recognizing perhaps some age appropriate or age conscious guidelines.
That's really important, and especially now that I'm a member of that older cohort. But when I was a younger onset rheumatologist before the era of biologics, there was this concept of elderly onset rheumatoid arthritis that oftentimes was seronegative. It was thought to be a more benign form of rheumatoid arthritis. The younger group had a lot of erosions, had high disease activity, rheumatoid nodules, which we don't usually see these days, and a lot of deformities. But the what they called elderly onset rheumatoid arthritis was thought to respond quite nicely to corticosteroids.
So I wonder some of the differences may be based on just the bias of practicing rheumatologists who are more likely to initiate corticosteroids for this older group. But the observation of erosions in this group suggests that maybe there was subclinical disease or at least not recognized disease that was ongoing for a longer period of time untreated resulting in the erosive change. But it's very nice that these patients are now being studied systematically. And certainly, the typical teaching is that about fifteen percent of patients with rheumatoid arthritis have a polymyalgia rheumatica like presentation. Given the age association of polymyalgia rheumatica, it's not surprising that this is the group which presents that way.
So very important abstract. Eric, what are your thoughts?
Yeah, I think it kind of goes full circle with what we talked about with the steroids that, I think a lot of physicians will see these patients and older often, but not always means comorbidities, and it means CHF and heart disease and diverticulitis and all these things that make people are afraid and they reach towards steroids, which are not safer. And I think we just need to understand disease control, inflammation, steroid use are things that are not helpful in elderly or older patients. And even more so than in the younger patient, we need to have steroids bearing treatment for them.
And Jeff, this is the BRASS cohort, which was the practice of the Brigham, which is a very rigorously trained group of rheumatologists. I trained there.
Thank you.
Longer ago than I wish to say. I think we were all trained in a similar way. Do you think that this cohort is representative of what's seen in other places?
Well, yes and no. You know, I think certainly these are people who are really interested in research and willing to, you know, participate in a very longitudinal cohort. But, you know, from talking to community rheumatologists, you know, they're definitely faced with this problem all the time. And I think I think the abstracts we picked all have nice themes related to, you know, really complex patients, and it's easy to get gun shy and to just turn towards glucocorticoids. And and as we've already talked about, that probably has long term consequences.
But have to say it's super interesting that these patients have so many erosions. They're probably, you know, been brushed off or maybe even internally, you know, just felt like they, you know, they're getting older, they have pain. And, I think there's definitely a lot of education that needs to happen even before rheumatology to try to find these patients. I think they don't fit the typical, picture about what you hear about in med school for rheumatoid arthritis. And as Jeeha's work has shown before, you know, these patients are undertreated for sure.
And often, you know, steroids are the crutch that happens and we all know the outcomes there.
Absolutely. So I'll kick off the lightning round with a very brief abstract or brief presentation of abstract number eight sixty seven. This was an oral presentation by Marc Blanchard from the Lausanne University Hospital in Lausanne, Switzerland, who's working with Thomas Hugel, is who one of the leaders of artificial intelligence and remote monitoring digital rheumatology. And this was the development of a remote patient monitoring system based on measuring the distance between finger skin folds. And as a joint becomes swollen, the finger skin folds become further apart from one another.
And so they developed this system where you take a picture of the fingers with an iPhone, the pixels where the skin folds are present are recognized and identified. And it measures the distance between these skin folds. And the wider the distance between skin folds, the more likely that that joint is to be swollen. So as we're faced with shortage of rheumatologists, longer wait to see a rheumatologist, less ability to accommodate follow-up visits. This is a way that patients might be able to take pictures of their fingers and assess progress in between visits.
Digital devices can be used to determine which patients might need to be seen sooner and which patients might be able to go further between visits. So very nice work being done in Lausanne, Switzerland about remote monitoring. Thoughts?
That's super cool. I never would have thought to do that. Now I wanna look before and after my turkey dinner on Thanksgiving to see how the finger folds are looking.
Yeah. And I guess for me, it would be more the abdominal folds than the finger fold. But this group also has a really neat app where they take a photograph of the hand and they measure excursion of the fingers as well as rate of excursion. And they can actually detect change. They took one patient, gave that patient an injection of one hundred and twenty milligrams of methylprednisolone.
And within days, there was a marked improvement that. So combination of these digital tools may be the future of rheumatology?
I think technology was a big part of this, and there were some good abstracts as well talking about using AI to try to identify patients that need to be seen sooner. I think what you framed it as a triage tool or a way to kind of help assess initially kind of who needs to be seen. Think if there's anything that our conversation so far has pointed is that I think things are too complex that I think the human brain is going to be needed. But I think the more information, the more data outside of clinic, we're all wearing on our watch all sorts of different data that can be helpful. And I think the more AI and digital applications, the more resources we have.
Well, there's gonna be so much data that it's gonna take AI to make sense out of that data.
I think the one thing to remember importantly is that when we get to tech based interventions like this, that it might exacerbate some existing disparities if people can't get access to these tools. Like, I mean, love the fact that it's real time at home and you're not just getting a point measure in the office, but I think we need to be conscious of the fact that it has to be equitable, accessible to all. But I think also the other is in the world when we're hearing a lot about the limitations workforce, it's something that can really aid in terms of improving the efficiency and access for our field. So I think overall, it's gonna be exciting to see how this gets integrated into our care system over the next couple of years.
And also what you talked about with older onset rheumatoid arthritis, my father is just a few months short of his one hundredth birthday. He has an eye, but he has great difficulty using it, both because of manual dexterity, but also cognitively as you get older. He was great with technology when he was in his 80s, but as you get close to 100, it's difficult. So older individuals may not be able to use this technology as well as younger individuals. Certainly, my grandsons at age five able to use technology that I can't even use.
So there is a disparity among individuals, even of the same socioeconomic group, but because of age and cognitive status. So who wants to go next?
I could talk about Michael Weinblack gave a good talk on abstract seventeen forty three, where they were comparing, basically asking a question that comes up often in clinic. I saw a couple of patients today in low disease activity. The question is, often we say remission is great, but low disease activity is good enough. Let's not uptitrate the medicines to the max. But what does that mean?
And they looked at comparing remission, which is at C. Dye under 2.8 to low disease activity is usually 2.8 to 10. But what if we do very low disease activity, 2.8 to six, or six to 10? And the short story is that patients who were six to 10 did not do as well as people under six, whether that's remission or that very low group, 2.8 to six. And so that was looked at looking at some of the PROs, the patient reported outcomes, and things like utilization of healthcare and ambulatory aids like CAINS.
And so, of course, it's not a huge surprise that patients who have higher disease activities don't do as well, but the fact that they're higher resource utilizers and it truly seems to be impacting their quality of life in their day to day, it really will make me think about those patients who are kind of chronically in that patient global of, or in that ZI of eight or nine, and maybe have a couple swollen joints that we may not be, we may be doing them a disservice by saying that they're in a good enough range.
So lower disease activity is better as long as it's not because you're treating them with steroids.
Right.
So Jeff.
Yeah, it probably matters, you know, the swollen joints versus patient global versus tender joint counts. Certainly, try to treat to zero swollen joints, but you can certainly I think it's really interesting data because I also worry about overtreatment for some people who have a high patient global that's not being driven by truly RA factors, but it sounds like the goal should be zero maybe.
I think the conversation around the target is interesting, but I have to agree with you, Jeff. If this is about the patient global, it may not be the DMARs that we need, especially when the outcome of interest was function, that it may be, you know, integrative medicine that we have guidelines for exercise, dietary changes. And it'd be interesting to see whether that not just the needle towards the remission.
Well, it's always important to try to figure out why the patient is hurting or why the patient is not functioning as well as they should. And as you point out, oftentimes it's not the rheumatoid arthritis, it's something else about
the- You can negotiate their patient global down to zero once you convince them it's due to something else. Without even needing a drug, that'd be great.
So, Jeff, what's your
Okay. My hot take lightning abstract is, I think it's $16.64. And honestly, I think this is gonna have the most longstanding ramifications for RA, and I think one of the best at the abstract. This is about spatial transcriptomics, which is truly cutting edge, and this was using the Accelerating Medicines Project. As you know, this has really delved into human tissue, trying to get the diseased organ and finding targets there as opposed to the old way of doing mouse models, curing it in mice and it not translating to people.
So in this study, they tracked down 30 synovial biopsies and had two different data sets, and the technology is just becoming really impressive now. You know, it's really getting as deep as possible at the moment into the granular nature about what's happening in synovium, which is really what's, you know, the organ that's that's diseased in RA. And as you've probably heard, spatial transchromatronics not only does single cell RNA sequencing, but it also keeps the spatial orientation of cells. So not only do you know what cells are, turned on and off and what bad actors there are, you can also know what the actual spatial arrangement is. Interacting with?
What physically are they near? Is it near vasculature? Is it near, you know, the actual synovium? Is it an interstitium? So to me, you know, this is really starting a spatial atlas.
And I will say that this abstract in particular not only just described what was going on, they did actually look at some interesting cell types and figured out some gene signatures and applied it to an external data set, and it seemed like that predicted treatment response. So I think even with these data, it's also important. But to me, is analogous. I think back in the eighties when I was watching the Magic School Bus inside the body traversing around. And then the other analogy is when when I first got Google Maps, like, I was just, you know, looking at neighborhoods all over the world.
You know? This is just like exploring uncharted territory, and I feel like this is gonna be a resource that's gonna be a game changer. And, certainly it's gonna be great that this is publicly available data so that other researchers can use their synovial biopsy programs and compare it to this. So to me, I think the possibilities are endless with this new technology.
Absolutely. When you were watching the Magic School Bus, all we had available to understand what was going on in the joint was the synovial fluid. And interestingly, I was in the lab at that time at the Brigham and collecting synovial fluid from rheumatoid arthritis patients. Nowadays, it's very rare that you see a rheumatoid arthritis patient with a joint effusion. And I would get maybe five or six synovial fluid samples a day, which
is Wow.
And now, you have to look to the synovium, which is a better place to look. But these synovial biopsies are very informative. Kospitallis in London doing the R4R study identifying subtypes of rheumatoid arthritis, it looks as if that twenty percent of patients who don't respond to traditional therapy have a fibroblast predominant phenotype. And we need to, we desperately need therapies that are going to address the synovial lining fibroblast. The AMP initiative is shedding light not only on rheumatoid arthritis, but also lupus.
And then AMP2 is psoriatic arthritis and Sjogren's syndrome. So this is an incredibly important collaborative effort. And this abstract exemplifies what we're learning. Spatial transcriptomics emphasize the importance of who are your neighbors as opposed to who's living in your house. So, Jeeha, you have the You last have the last choice for the lightning round.
Wonderful. I'm going to bring us back to the importance of treat to target and a little bit about the steroids. So the abstract number is sixteen forty seven. It's about improved fertility in women with RA, and how to target can be an approach for that. So this is a Dutch based study, and this group used a cohort called the Para Cohort, where women intending to get pregnant or were in their first trimester were in their usual care.
And then they had a second cohort called Pre Cara, which was the same kind of demographic, but they had a treat to target approach. And in addition to that, they were, using TNFs when appropriate, but they would not use NSAIDs or prednisone. And that's because they'd shown that women with RA are twice as likely to experience fertility issues compared to women without. And some of the factors that contribute to that is age and nulliparity, which we know about, but it's disease activity, the use of NSAIDs and the use of prednisone. So they have these two cohorts to compare whether usual care versus treat to target with some consideration for other medications can improve outcomes.
And the results were really promising. In terms of the time to conceive, those in the pre care of the one with the treat to target, it took about a median of eighty four days compared to one hundred and ninety six days in the PERIC cohort. So that's almost double the time for the group of women who didn't get treated to target. And also in terms of the proportion of women who could not get pregnant, it was much lower. In the pre CARA, basically, three out of four women were able to conceive within the first year, whereas it was only one in two for the para cohort.
So think this is a, know, RA not only does it affect function, but for women, there's real conversations to be had about fertility, especially when we give medications that are teratonic. And we think about that, about in terms of prescribing, but I think we need to be aware that by achieving treat to target, again, that work can actually improve fertility. And I just want to draw to the attention that we have guidelines about how to prescribe medications. And one thing I like about that guideline is that it not only talks about how to prescribe medication for women planning to get pregnant, but there's also a section about men planning to father children. I've had patients, male patients ask me this about, What can I do to make sure that we can expand our family?
So I think this is a really important piece of conversation and the thought process we should have.
Absolutely. Did they separate out whether it was physical function that improved, that allowed for conception, or was it an endocrinologic effect, or both?
They didn't get to that, and they also didn't get to the difference between remission versus LDA, although they had both of that as the goal.
So an important study from Rotterdam. The Netherlands has been incredibly productive over the past quarter century, probably because it's a small country with six major medical centers, each of which is focused on a different aspect of rheumatology so that they've competed in a friendly way, but not really stepped on each other's toes. And I've visited The Netherlands a number of times I've studied on clinics. First of all, patients live close by. They bicycle to the clinic.
They get their CRP drawn, and their joints are examined by a metrologist. And when they send to the rheumatologist, the rheumatologist is sitting on one side of a desk. The patient hands the rheumatologist their joint count. The CRP is already back, and they've got a DAS28 calculated. The Netherlands has really advanced a lot of what we know about rheumatology.
The surrounding rheumatologists at each major medical center have a good relationship with that medical center. And because it's a capitated system, they don't lose money by having their patients followed by the academic medical center for clinical trials. So in The United States, we have a lot to learn from The Netherlands about how to do clinical research successfully. Well, you guys have done a tremendous job, not only tonight, but also a lot of hard work covering rheumatoid arthritis for RheumNow during ACR Convergence twenty twenty four. Thank you for that and for your participation in this roundtable.
And for more about rheumatoid arthritis, go to roomnow.com. I'm Jonathan K. With Eric Dine and Jee Lee and Jeff Sparks.
Yes. Hi, I'm Eric Dyne. I'm from Atlantic Health in Summit, New Jersey.
Jeeha?
Hi, my name is Jeeha Lee. I'm a rheumatologist from University of Michigan.
And finally, Jeff.
Hey, everyone. My name is Jeff Sparks. I'm a rheumatologist at Brigham Women's Hospital and Harvard Medical School in Boston, Massachusetts.
Excellent. So for the first round, each of us is going to pick our favorite abstract. So Eric, what piqued your interest?
So I'm going to talk about abstract seventeen forty five. I think there I don't know if there's oral surveillance fatigue after talking about it endlessly at our prior conferences, but I thought there was one post hoc analysis looking back at it that I thought was useful and changes the way I think about that data a little bit. And so, this was looking at, of course, who have been following know that the oral surveillance was looking at tofacitinib versus adalimumab. And of course, that main takeaway is that there was the higher cancer and MACE event in those at risk patients on tofacitinib compared to TNF inhibitor like adalimumab. That, of course, has had a lot of conversation, the black box warning, and a lot of conversation who is appropriate for tofacitinib and how do we interpret that slightly higher increased risk.
One thing that I thought was interesting was when they specifically looked at the statins usage of patients on it. This is a study that was enriching for patients at the highest risks that were they were looking for outcomes, and yet under a quarter of them were on a baseline statin. Of patients in the study who had known ASCVD, so should be on a statin, Only fifty three percent were on it, so about half of them were on it. Only about fourteen percent of people were on the high intensity ideal statin. So it was certainly not optimized in these patients in a clinical trial.
And I thought what was interesting, the main kind of takeaway of it, is that when you look at the patients who were on a statin in the tofacitinib group compared to the people on the statin in adalimumab, so ideally the people who are getting the ideal management, there wasn't a difference in MACE events. What does this mean? Think kind of the first takeaway is we need to be doing more to make sure that we're doing that baseline therapy. Of course, when we go into these post hoc analyses, you're cutting and dicing the numbers in all sorts of different ways and you could find all sorts of noise in the numbers. So, I want to take this as absolute faith, but it is reassuring to say that if we're managing the comorbidities and we're doing all the preventative things, maybe that might mitigate it.
And when we're thinking about weighing the risks and benefits in a patient who we think may be on a JAK inhibitor or appropriate for a JAK inhibitor but has some risk factors, would, as I'm weighing that, I would say, let's at least make sure that we're doing that right therapy. So, I think that's an interesting way to look at that study and those risks.
So that's an interesting study. It reflects that rheumatologists are not necessarily doing a great job of putting our patients on statins, But rheumatologists are quite busy. And in the twenty minutes that you have with a patient with rheumatoid arthritis who's on methotrexate and probably another disease modifying antirheumatic drug, you know, do you have time to talk about the statins and talk about everything else? We should. But I think we're all in the dark about that.
And Eric, it looks like you're in the dark, too. But as you come into the light, rheumatologists should come into the light and think more about prescribing statins for patients with rheumatoid arthritis at increased risk for cardiovascular disease, at least those taking a JAK inhibitor. Jeff, what are your Well,
first off, I chatted with John about this and he promised me it would be the last oral surveillance post hoc analysis. I'm gonna hopefully hold him to that, but I doubt that, but probably be a lot more. I have to say, it's pretty shocking that patients enrolled into a clinical trial for cardiovascular disease, the outcome that so few people were on statins that should have been. And we all know it's even worse in clinical care. And these are complex patients.
They're falling through the cracks. They get fragmented care. So obviously a huge opportunity to get patients to get treated appropriately. And I think as Eric hit the nail on the head, I think you feel a lot more reassured to start a JAK inhibitor in someone that's on a statin. So I think this is a really high impact abstract.
Absolutely, geeha.
No, I agree with that. And I think one of the themes I saw throughout ACR was more and more emphasis about treating the whole patient, really taking into the fact all their multimorbidity. That's one of the things that Doctor. McGinnis talked about even starting at the review course, because there's data to show with each multimorbidity effectiveness, the DMARs go down and also our patients become more difficult to treat with more, not only just the disease activity related burden, but also the uncontrolled symptoms like fatigue and pain. So I think overall I hear and resonate with you that it's sometimes perhaps out of the scope rheumatology, given the time limited barriers we have, but this is all the more reason why generating this data is important, but then to be able to have something embedded in our electronic health record system that makes it easier to identify these patients, but actually really design care models that allow for a comprehensive care model.
And oral surveillance enrolled older patients. So these are patients who not only have rheumatoid arthritis, but having been around for at least fifty years and having at least one cardiovascular risk factor, this is a patient population that we should pay specific attention to. So especially in the older patient, although I regard 50 as being rather young, but it's all relative. But that's a population in which we should do a better job of reducing cardiovascular risk. While we're on the topic of cardiovascular risk, I might as well take a shot at my abstract.
I'm going to pick abstract number 2,673, which was presented at the oral rheumatoid arthritis treatment session, the last session of the meeting on Tuesday morning between 11AM and 12:30PM. John Giles and I co chaired that session. And this was an abstract from British Columbia. It was an abstract that looked at changes in mortality risk after stopping glucocorticoids. In British Columbia, there's a single payer and a large population based cohort of patients with rheumatoid arthritis.
They took this population based incident rheumatoid arthritis cohort of patients who met the definition of having rheumatoid arthritis using nineteen eighty seven ACR criteria between 01/01/1996 and December 3133. So in 2010, the ACR ULAAR criteria came out, but this used the older ACR criteria. And they used billing data that followed these patients until the December 2018. And they looked at oral glucocorticoid exposure, yes or no. And they looked at deaths with cardiovascular disease or infections as the primary cause, identifying those from death certificates.
And they looked at the risk of death associated with cumulative duration of glucocorticoid use and time since glucocorticoid cessation. And what was most impressive, the key finding was that the mortality due to cardiovascular disease or due to infections never returned to normal for individuals who had been taking glucocorticoids for longer than two years in terms of cardiovascular death or for longer than three years in terms of infections. So, if you'd use glucocorticoids for six, twelve, or twenty four months for cardiovascular deaths, your risk returned to the level of those who've never been exposed to glucocorticoids at two point five years for those who'd been treated with glucocorticoids for six months, three point five years for those who'd been treated for one year, and at five point five years for those who had been treated for two years with glucocorticoids. But the most impressive finding was that if you'd been on glucocorticoids for longer than two years and certainly longer than three years, the increased mortality risk from cardiovascular disease and infection persisted. So glucocorticoids are not trivial in the least.
The infection related mortality increased by seven point five percent for every year of glucocorticoid use and decreased by one point three percent for every year after stopping glucocorticoids. That from infections increased by six point eight percent for every year of glucocorticoid use and decreased by four point nine percent for every year after stopping glucocorticoids. So patients who are treated for just a brief six month period, which is not uncommon to control disease activity in someone starting disease modifying antraumatic drug, those patients have significantly increased cardiovascular death and also death due to infections. So we have to be very mindful of the potential risks that we're imparting by prescribing glucocorticoids. And we have to be as prompt as possible in discontinuing these medications.
This was a concurrent session, but this abstract certainly has the impact that it should have been a plenary.
I agree. I think there was actually a scientific session about envisioning a steroid free remission and the topic wasn't just about RA, but there was discussion around vasculitis as well as lupus. So this shift in terms of recognizing that steroids, that it's not just the duration, but that even at very low doses, and also like this study pointed out that there are long lasting negative effects is becoming recognized. Michele Petrie in the lupus literature said for every one milligram, there's a three percent increased risk of organ damage. And like one milligram, that's pretty trivial.
And one of the things I took away from this study and that session discussion is that continuation is an action that if we don't pay attention to the medication they're beyond, and then we might be missing opportunity whereby escalating therapy, they would have better chances of tapering off of steroids. Beth Wallace studies this area, and she's shown time and again that tapering is really challenging, not just because of adrenal sufficiency related reasons, but they also develop steroid withdrawal symptoms that are quite different from disease activity. So there's a lot of challenges. We don't know how yet to get there. So I think what's important is for us to recognize that we need to reduce the pipeline so that less people end up on these low dose steroids.
So that means earlier on, we need to really make sure that we assess the burden and treat patients according to the newer regimens that are available. Because I think, Jeff, you did this study to show that there were actually very habitual. No matter how many new DMARs are introduced into the market, HUMIRA has the largest share and there's a delay of any new DMARs and then the numbers really don't blip. That was really fascinating for me.
I'm glad you used the term habituals because I was going to say that corticosteroids are addictive. They are. And I have a patient who called me yesterday. I started him on methotrexate. He was new onset rheumatoid arthritis.
I started him on methotrexate about four or five months ago. Initially treated him with methotrexate escalated quickly to twenty five milligrams a week, put him on a TNF inhibitor. After three months on alimab, his disease remained active. So I switched him I put him in the RA proper study. So the study randomized him to a non TNF biologic rather than a JAK inhibitor.
But I put him on abatacept. And he's only been on abatacept for about a month, but he called up saying that his hands were miserable. He's a tailor, and he has to work with his hands, and he's been unable to work for the week. So I put him on steroids. But he's been on a number of steroid tapers because he can't function and can't work without that.
But the impact that the steroids that I'm prescribing in the best interest of the patient are also not in his best interest in terms of increasing his risk of cardiovascular and death from infection cardiovascular death and death from infection. So I certainly want him to live and I want him to be comfortable. But it's we're really navigating a narrow channel between Scylla and Charybdis as did Adesha's in Odyssey.
I love it. Wow.
Anyhow, Jeff, you've got an abstract there.
Well, was just going to chime in that, you know, I think this has been the theme over the last five, ten years. You know, it reminds me of the Ralph Nader book, Unsafe at Any Speed. And we'd love to hate steroids, but it seems like we haven't put a dent in it. And part of this is going back to the guideline debate, ACR, I was on that guideline and we, I think bravely said that the default should not be to use glucocorticoids and many other guidelines say you should use it. And I think everyone knows that there's long term toxicity, but I think you can't be a long term user unless you start.
So short term glucocorticoid use as a gateway drug, if you will. So anyway, I think this is the eternal debate in rheumatology about love and hate relationship with steroids.
Well, we're giving the initial dose of crack cocaine. You put the patient on
I'm not prescribing that. Just
No, not literally, but we're the dealer. We're giving them a taste of what it's like.
We should give them less refills, perhaps.
Yeah. I think Johnstone Cold Steroids are a necessary evil in rheumatology.
Yeah, Doctor. Petrie always says that the P is for poison, for prednisone.
They seem impervious to all this bad press. I don't know if there's any other analogy going on.
Well, and I don't give refills on methotrexate prescriptions. I'll give a ninety one day prescription that'll last just thirteen weeks. But we ought to think very carefully as you suggested that we not give refills on prednisone and that we reassess each time that we're refilling a corticosteroid prescription.
And patients will stockpile is the other kind of big takeaway from that scientific session is when you start prednisone, have to have an end date, you have to have a plan. They talk about withdrawing or tapering quickly, withdrawing the last doses more slowly so that you're dealing with those withdrawal effects. But really having a plan, knowing how much they have, how much they're taking so that they don't have these emergency supplies so that they're self medicating.
Yeah. And I think that's important, like you said, making sure to have an awareness and document, because actually now documenting a taper plan is a CMS quality measure. So there's a system level recognition of this issue, and there's gonna be, I think, more scrutiny and efforts to be able to address this, not just for rheumatology, but across the board.
So the patient who asks to have a Medrol dose pack in reserve, just in case they have a flare, we should probably think very carefully before writing that prescription.
Yep.
So Jeff, you've got another abstract there.
All
right. Well, I couldn't resist an RAILD abstract. I'm sorry. But I am gonna talk about abstract number seventeen thirteen. I think this was the most important abstract for RA at the meeting.
This was about treatment of RA ILD with biologic and targeted synthetic DMARDs. So this is VA data led by the Nebraska group with Bryant England, and, you know, they're doing great work. And they looked at their VA database. As we all know, it's more men, it's more smokers. So maybe not generalizable, but it's really enriched for RAILD.
So it's a great data set for that. So they previously validated methods to find RAILD, and in this analysis, they looked at new users of biologic and targeted synthetic DMARDs who had RAILD and did target trial emulation. For those that don't know, this is kind of the cutting edge epidemiologic technique to try to really use observational data to do as best as you can to do kind of a head to head comparison, kind of a dream RCT, if you will. So in this study, they looked at all the different mechanisms of action, compared it to rituximab. As a side note, the 2023 ACR chest guidelines, recommended rituximab as first line treatment for RA ILD, and none of these other medications were recommended as first line treatment, so we really need some data here.
And really, the the bottom line is is that there were no statistical, associations with the outcomes, which were very important outcomes of respiratory hospitalization or overall mortality. So that's comparing abatacept to rituximab, comparing, IL-six receptor inhibitors to rituximab, and comparing abatacept, TNF inhibitors, as well as JAK inhibitors. So no difference whatsoever across all of those categories. And certainly it could be underpowered. It could be a hard outcome to hit.
It could be that all the drugs we're using actually work to prevent these bad outcomes. It could be that none of them work. And certainly it could be related to confounding where maybe even though these patients have RALD, there's certainly a spectrum of severity. Maybe some people are more active in the joints and they're choosing one of the meds for that. Maybe the rituximab's treating the really, really bad RA ILD.
But I think it's really the most comprehensive analysis that's been done looking at DMARDs and RA ILD treatment. And as an aside, our group recently reviewed all of the trial data that informed the, ACR chest guidelines. And even though RA is our most common disease, this is one of the most serious manifestations. There's actually only ever been three trials that have enrolled any RALD patients into a prospective trial. So, to me, it's just, you know, huge, huge, opportunity and gap in literature because we're certainly confronted with these patients and certainly our group and others are moving towards trial, and this will be a great sort of lead into that.
Excellent. So it doesn't really matter what you choose as long as you're treating the disease.
You know, I think the optimist view is that, and I have to say the pulmonologists say this as well, you know, they have RA that's driving the lung disease. If you treat the RA successfully, that's also going to treat the lungs. I think that's the optimistic view. I think the pessimistic view is that none of them work. And again, I think another certainly possible outcome is that perhaps it's a confounding issue where the really bad patients got rituximab and maybe it helped those patients and then the very mild patients got the alternative drugs and it didn't really, there wasn't much to be needed as far as to be helped.
So, yeah, like I said, I think it's a really nice framework that leads to kinda more definitive trials, and we really need it, honestly. We have a few antifibrotics, but, you know, this is not an uncommon, thing to be confronted with in care. And it's just really frustrating, as you know, to see these patients, you know, progress into worse and, you know, we're not sure how our drugs are helping or hurting in the end.
Well, to get back to anecdotal medicine, I have a patient with rheumatoid arthritis. I've followed him probably about twenty years and he was doing fine on methotrexate and on, I think, etanercept. And all of a sudden he had some shortness of breath and went to the local hospital, was found to have ILD. And now he's in hospice care.
Yeah. It's really humbling when you see this. Yeah, it's really, really tough.
And I treat rheumatoid arthritis disease activity aggressively, so his RH disease activity was well controlled. Yeah. I could have done more for him.
Yeah, certainly it's more complicated than just, you know, treating to target, getting them into remission from a joint standpoint. We certainly see many patients that continue to have lung disease.
Are there any of the biologic DMARDs that might have a little bit worse safety profile in terms of lung disease?
Well, you know, TNF inhibitors have probably a reputation for not being good for the lungs and probably not helping. And actually the same group last year did a very similar abstract that was presented at the plenary looking at TNF inhibitors versus alternative biologics, and they also did not find any difference in outcomes. And, again, I think it is reassuring when you have to reach for it to have some data saying that this isn't gonna, you know, really blossom their ILD and worsen things. But, you know, during the day, we really wanna know what's gonna treat it and what's the best option.
Well, we look forward to the excellent work that's coming out of your group and look to you and your colleagues for leadership. So Jihai, your last abstract in the first round before the lightning round. So what happens in your interest?
Yeah. So Justice Jack is partial to ILD. I am partial to aging related issues in rheumatology. So I'm going to discuss abstract number 2,224, which looks at the age of onset of RA and radiographic changes. This study used data out of, Brigham, but interesting, the first author is, from Japan, which I think is meaningful because Japan has one of the oldest aging populations, so they actually have a lot of data about this.
So this study focused on an entity known as late onset RA, which means a person is diagnosed with RA typically over the age of 65. And they had a longitudinal cohort, called BRAS, the Brigham Women's Hospital Rheumatoid Arthritis Sequential Study, which is a single center, large RA registry, which means you have disease activity measures demographics. This is valuable because older adults are usually excluded from clinical trials, so to be able to have a data set where you can directly compare older adults to younger provides value because otherwise you're limited to using claims or administrative data to study older adults in that regard. And so what they were specifically interested in was are there differences in terms of incident radiographic changes? And the reason is because this entity of late onset started actually appearing in the literature Okay, Google.
Okay,
Google, turn on lights.
1950s to the 1960s. But we really don't recognize this in clinical practice. But then last year, our European colleagues published paper looking at incidents of rheumatic diseases across the board. They had more than two million patients, registered, and it showed that the peak incidence of RA has somewhat shifted, and we're seeing people diagnosed actually into their 70s and 80s. So there's a growing group of older adults newly being diagnosed with RA, and we know they have very different clinical presentations.
They tend to have more acute onset, systemic presentations, large joint involvement, CR negativity. And we talked earlier about, multimorbidity and it's pulling the challenge for us as rheumatologists because we're having to introduce high risk medication to an older adult who already has existing multimorbidities. So I think this population in particular poses interesting challenges. And what they found is they had patients diagnosed based on their age of already diagnosis, split them up as young if they were diagnosed on 44 years of age or younger, middle if they were 45 to 65, and anybody diagnosed after the age of 66 was considered late onset. And in that group for that late onset, the average age was around 72.
And what's interesting is that when you become late onset, the sex disparity that we typically see in the younger population kind of diminishes. So about fifty percent were female in that late onset group compared to like eighty to ninety percent in the younger two age groups as well. And as I mentioned before, they tend to be more seronegative if they have late onset RA. This group did have higher disease activity measures on diagnosis, but at the same time they were less likely to receive DMARS, especially biologics or targeted synthetics. So only about ten percent of the late onset RA were on biologics, whereas the younger groups, about twenty to twenty five percent were on it.
And conversely, that also meant that the late onset group were more on steroids, about fifty percent were on steroids as opposed to only about a third, in the younger age groups. In terms of that outcome that they were interested in terms of erosions, when they did, odds ratio calculations and multivariable analysis compared to the young onset, the late onset were eight times more likely to have erosive changes near and at the time of diagnosis. And this actually persisted even when they adjusted for treatment. So when you were without any treatment, the odds went down a little bit to six, but if you didn't, it went up to 10. So there's still quite of a disparity in terms of disease severity in terms of presentation based on disease activity, but unknowingly they also are going to be more likely to approve erosion and damage.
So I think that it's important to recognize that this entity exists in terms of late onset RA, that they can have very different presentation. Not included in this paper, but reported in others, is that there's a lot of overlap with PMR, about a third have that phenotype, and another third will actually have OA type phenotype. So that can lead to delays in diagnoses. But I think that awareness is going to allow us to say, okay, this is also another population where we need to check some of our biases because there was a study where, the rheumatologist said erosions are, they consider erosion to be as important as age in terms of determining treatment decisions. But if you see the older number age, they're four times likely to initiate any kind of DMARC.
So I think we need to start recognizing how we perceive age, that it's not just a number, but to ensure that we actually introduce treatments in this population and start recognizing perhaps some age appropriate or age conscious guidelines.
That's really important, and especially now that I'm a member of that older cohort. But when I was a younger onset rheumatologist before the era of biologics, there was this concept of elderly onset rheumatoid arthritis that oftentimes was seronegative. It was thought to be a more benign form of rheumatoid arthritis. The younger group had a lot of erosions, had high disease activity, rheumatoid nodules, which we don't usually see these days, and a lot of deformities. But the what they called elderly onset rheumatoid arthritis was thought to respond quite nicely to corticosteroids.
So I wonder some of the differences may be based on just the bias of practicing rheumatologists who are more likely to initiate corticosteroids for this older group. But the observation of erosions in this group suggests that maybe there was subclinical disease or at least not recognized disease that was ongoing for a longer period of time untreated resulting in the erosive change. But it's very nice that these patients are now being studied systematically. And certainly, the typical teaching is that about fifteen percent of patients with rheumatoid arthritis have a polymyalgia rheumatica like presentation. Given the age association of polymyalgia rheumatica, it's not surprising that this is the group which presents that way.
So very important abstract. Eric, what are your thoughts?
Yeah, I think it kind of goes full circle with what we talked about with the steroids that, I think a lot of physicians will see these patients and older often, but not always means comorbidities, and it means CHF and heart disease and diverticulitis and all these things that make people are afraid and they reach towards steroids, which are not safer. And I think we just need to understand disease control, inflammation, steroid use are things that are not helpful in elderly or older patients. And even more so than in the younger patient, we need to have steroids bearing treatment for them.
And Jeff, this is the BRASS cohort, which was the practice of the Brigham, which is a very rigorously trained group of rheumatologists. I trained there.
Thank you.
Longer ago than I wish to say. I think we were all trained in a similar way. Do you think that this cohort is representative of what's seen in other places?
Well, yes and no. You know, I think certainly these are people who are really interested in research and willing to, you know, participate in a very longitudinal cohort. But, you know, from talking to community rheumatologists, you know, they're definitely faced with this problem all the time. And I think I think the abstracts we picked all have nice themes related to, you know, really complex patients, and it's easy to get gun shy and to just turn towards glucocorticoids. And and as we've already talked about, that probably has long term consequences.
But have to say it's super interesting that these patients have so many erosions. They're probably, you know, been brushed off or maybe even internally, you know, just felt like they, you know, they're getting older, they have pain. And, I think there's definitely a lot of education that needs to happen even before rheumatology to try to find these patients. I think they don't fit the typical, picture about what you hear about in med school for rheumatoid arthritis. And as Jeeha's work has shown before, you know, these patients are undertreated for sure.
And often, you know, steroids are the crutch that happens and we all know the outcomes there.
Absolutely. So I'll kick off the lightning round with a very brief abstract or brief presentation of abstract number eight sixty seven. This was an oral presentation by Marc Blanchard from the Lausanne University Hospital in Lausanne, Switzerland, who's working with Thomas Hugel, is who one of the leaders of artificial intelligence and remote monitoring digital rheumatology. And this was the development of a remote patient monitoring system based on measuring the distance between finger skin folds. And as a joint becomes swollen, the finger skin folds become further apart from one another.
And so they developed this system where you take a picture of the fingers with an iPhone, the pixels where the skin folds are present are recognized and identified. And it measures the distance between these skin folds. And the wider the distance between skin folds, the more likely that that joint is to be swollen. So as we're faced with shortage of rheumatologists, longer wait to see a rheumatologist, less ability to accommodate follow-up visits. This is a way that patients might be able to take pictures of their fingers and assess progress in between visits.
Digital devices can be used to determine which patients might need to be seen sooner and which patients might be able to go further between visits. So very nice work being done in Lausanne, Switzerland about remote monitoring. Thoughts?
That's super cool. I never would have thought to do that. Now I wanna look before and after my turkey dinner on Thanksgiving to see how the finger folds are looking.
Yeah. And I guess for me, it would be more the abdominal folds than the finger fold. But this group also has a really neat app where they take a photograph of the hand and they measure excursion of the fingers as well as rate of excursion. And they can actually detect change. They took one patient, gave that patient an injection of one hundred and twenty milligrams of methylprednisolone.
And within days, there was a marked improvement that. So combination of these digital tools may be the future of rheumatology?
I think technology was a big part of this, and there were some good abstracts as well talking about using AI to try to identify patients that need to be seen sooner. I think what you framed it as a triage tool or a way to kind of help assess initially kind of who needs to be seen. Think if there's anything that our conversation so far has pointed is that I think things are too complex that I think the human brain is going to be needed. But I think the more information, the more data outside of clinic, we're all wearing on our watch all sorts of different data that can be helpful. And I think the more AI and digital applications, the more resources we have.
Well, there's gonna be so much data that it's gonna take AI to make sense out of that data.
I think the one thing to remember importantly is that when we get to tech based interventions like this, that it might exacerbate some existing disparities if people can't get access to these tools. Like, I mean, love the fact that it's real time at home and you're not just getting a point measure in the office, but I think we need to be conscious of the fact that it has to be equitable, accessible to all. But I think also the other is in the world when we're hearing a lot about the limitations workforce, it's something that can really aid in terms of improving the efficiency and access for our field. So I think overall, it's gonna be exciting to see how this gets integrated into our care system over the next couple of years.
And also what you talked about with older onset rheumatoid arthritis, my father is just a few months short of his one hundredth birthday. He has an eye, but he has great difficulty using it, both because of manual dexterity, but also cognitively as you get older. He was great with technology when he was in his 80s, but as you get close to 100, it's difficult. So older individuals may not be able to use this technology as well as younger individuals. Certainly, my grandsons at age five able to use technology that I can't even use.
So there is a disparity among individuals, even of the same socioeconomic group, but because of age and cognitive status. So who wants to go next?
I could talk about Michael Weinblack gave a good talk on abstract seventeen forty three, where they were comparing, basically asking a question that comes up often in clinic. I saw a couple of patients today in low disease activity. The question is, often we say remission is great, but low disease activity is good enough. Let's not uptitrate the medicines to the max. But what does that mean?
And they looked at comparing remission, which is at C. Dye under 2.8 to low disease activity is usually 2.8 to 10. But what if we do very low disease activity, 2.8 to six, or six to 10? And the short story is that patients who were six to 10 did not do as well as people under six, whether that's remission or that very low group, 2.8 to six. And so that was looked at looking at some of the PROs, the patient reported outcomes, and things like utilization of healthcare and ambulatory aids like CAINS.
And so, of course, it's not a huge surprise that patients who have higher disease activities don't do as well, but the fact that they're higher resource utilizers and it truly seems to be impacting their quality of life in their day to day, it really will make me think about those patients who are kind of chronically in that patient global of, or in that ZI of eight or nine, and maybe have a couple swollen joints that we may not be, we may be doing them a disservice by saying that they're in a good enough range.
So lower disease activity is better as long as it's not because you're treating them with steroids.
Right.
So Jeff.
Yeah, it probably matters, you know, the swollen joints versus patient global versus tender joint counts. Certainly, try to treat to zero swollen joints, but you can certainly I think it's really interesting data because I also worry about overtreatment for some people who have a high patient global that's not being driven by truly RA factors, but it sounds like the goal should be zero maybe.
I think the conversation around the target is interesting, but I have to agree with you, Jeff. If this is about the patient global, it may not be the DMARs that we need, especially when the outcome of interest was function, that it may be, you know, integrative medicine that we have guidelines for exercise, dietary changes. And it'd be interesting to see whether that not just the needle towards the remission.
Well, it's always important to try to figure out why the patient is hurting or why the patient is not functioning as well as they should. And as you point out, oftentimes it's not the rheumatoid arthritis, it's something else about
the- You can negotiate their patient global down to zero once you convince them it's due to something else. Without even needing a drug, that'd be great.
So, Jeff, what's your
Okay. My hot take lightning abstract is, I think it's $16.64. And honestly, I think this is gonna have the most longstanding ramifications for RA, and I think one of the best at the abstract. This is about spatial transcriptomics, which is truly cutting edge, and this was using the Accelerating Medicines Project. As you know, this has really delved into human tissue, trying to get the diseased organ and finding targets there as opposed to the old way of doing mouse models, curing it in mice and it not translating to people.
So in this study, they tracked down 30 synovial biopsies and had two different data sets, and the technology is just becoming really impressive now. You know, it's really getting as deep as possible at the moment into the granular nature about what's happening in synovium, which is really what's, you know, the organ that's that's diseased in RA. And as you've probably heard, spatial transchromatronics not only does single cell RNA sequencing, but it also keeps the spatial orientation of cells. So not only do you know what cells are, turned on and off and what bad actors there are, you can also know what the actual spatial arrangement is. Interacting with?
What physically are they near? Is it near vasculature? Is it near, you know, the actual synovium? Is it an interstitium? So to me, you know, this is really starting a spatial atlas.
And I will say that this abstract in particular not only just described what was going on, they did actually look at some interesting cell types and figured out some gene signatures and applied it to an external data set, and it seemed like that predicted treatment response. So I think even with these data, it's also important. But to me, is analogous. I think back in the eighties when I was watching the Magic School Bus inside the body traversing around. And then the other analogy is when when I first got Google Maps, like, I was just, you know, looking at neighborhoods all over the world.
You know? This is just like exploring uncharted territory, and I feel like this is gonna be a resource that's gonna be a game changer. And, certainly it's gonna be great that this is publicly available data so that other researchers can use their synovial biopsy programs and compare it to this. So to me, I think the possibilities are endless with this new technology.
Absolutely. When you were watching the Magic School Bus, all we had available to understand what was going on in the joint was the synovial fluid. And interestingly, I was in the lab at that time at the Brigham and collecting synovial fluid from rheumatoid arthritis patients. Nowadays, it's very rare that you see a rheumatoid arthritis patient with a joint effusion. And I would get maybe five or six synovial fluid samples a day, which
is Wow.
And now, you have to look to the synovium, which is a better place to look. But these synovial biopsies are very informative. Kospitallis in London doing the R4R study identifying subtypes of rheumatoid arthritis, it looks as if that twenty percent of patients who don't respond to traditional therapy have a fibroblast predominant phenotype. And we need to, we desperately need therapies that are going to address the synovial lining fibroblast. The AMP initiative is shedding light not only on rheumatoid arthritis, but also lupus.
And then AMP2 is psoriatic arthritis and Sjogren's syndrome. So this is an incredibly important collaborative effort. And this abstract exemplifies what we're learning. Spatial transcriptomics emphasize the importance of who are your neighbors as opposed to who's living in your house. So, Jeeha, you have the You last have the last choice for the lightning round.
Wonderful. I'm going to bring us back to the importance of treat to target and a little bit about the steroids. So the abstract number is sixteen forty seven. It's about improved fertility in women with RA, and how to target can be an approach for that. So this is a Dutch based study, and this group used a cohort called the Para Cohort, where women intending to get pregnant or were in their first trimester were in their usual care.
And then they had a second cohort called Pre Cara, which was the same kind of demographic, but they had a treat to target approach. And in addition to that, they were, using TNFs when appropriate, but they would not use NSAIDs or prednisone. And that's because they'd shown that women with RA are twice as likely to experience fertility issues compared to women without. And some of the factors that contribute to that is age and nulliparity, which we know about, but it's disease activity, the use of NSAIDs and the use of prednisone. So they have these two cohorts to compare whether usual care versus treat to target with some consideration for other medications can improve outcomes.
And the results were really promising. In terms of the time to conceive, those in the pre care of the one with the treat to target, it took about a median of eighty four days compared to one hundred and ninety six days in the PERIC cohort. So that's almost double the time for the group of women who didn't get treated to target. And also in terms of the proportion of women who could not get pregnant, it was much lower. In the pre CARA, basically, three out of four women were able to conceive within the first year, whereas it was only one in two for the para cohort.
So think this is a, know, RA not only does it affect function, but for women, there's real conversations to be had about fertility, especially when we give medications that are teratonic. And we think about that, about in terms of prescribing, but I think we need to be aware that by achieving treat to target, again, that work can actually improve fertility. And I just want to draw to the attention that we have guidelines about how to prescribe medications. And one thing I like about that guideline is that it not only talks about how to prescribe medication for women planning to get pregnant, but there's also a section about men planning to father children. I've had patients, male patients ask me this about, What can I do to make sure that we can expand our family?
So I think this is a really important piece of conversation and the thought process we should have.
Absolutely. Did they separate out whether it was physical function that improved, that allowed for conception, or was it an endocrinologic effect, or both?
They didn't get to that, and they also didn't get to the difference between remission versus LDA, although they had both of that as the goal.
So an important study from Rotterdam. The Netherlands has been incredibly productive over the past quarter century, probably because it's a small country with six major medical centers, each of which is focused on a different aspect of rheumatology so that they've competed in a friendly way, but not really stepped on each other's toes. And I've visited The Netherlands a number of times I've studied on clinics. First of all, patients live close by. They bicycle to the clinic.
They get their CRP drawn, and their joints are examined by a metrologist. And when they send to the rheumatologist, the rheumatologist is sitting on one side of a desk. The patient hands the rheumatologist their joint count. The CRP is already back, and they've got a DAS28 calculated. The Netherlands has really advanced a lot of what we know about rheumatology.
The surrounding rheumatologists at each major medical center have a good relationship with that medical center. And because it's a capitated system, they don't lose money by having their patients followed by the academic medical center for clinical trials. So in The United States, we have a lot to learn from The Netherlands about how to do clinical research successfully. Well, you guys have done a tremendous job, not only tonight, but also a lot of hard work covering rheumatoid arthritis for RheumNow during ACR Convergence twenty twenty four. Thank you for that and for your participation in this roundtable.
And for more about rheumatoid arthritis, go to roomnow.com. I'm Jonathan K. With Eric Dine and Jee Lee and Jeff Sparks.
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